Chloroquine (Oral)

Chloroquine is an antimalarial medication that has been used to prevent and treat malaria since World War II. In recent years, its effectiveness has been limited due to the development of resistant strains of malaria probably stemming from the mass distribution of chloroquine during and after World War II across geographic regions known to foster malaria.

Overview

Discovered in 1934 by German scientist Hans Andersag, chloroquine (also marketed at Resochin, Aralen, chloroquine FNA and Dawaquin) has been used since World War II for the treatment of malaria. It is a member of the class of drugs called 4-aminoquinolines and was originally thought to be too dangerous to use with humans. However, during the war, experiments conducted by the United States proved chloroquine to be an effective agent in both treatment and prevention of malaria. Prophylactic use of chloroquine to prevent malaria began in 1947.

Chloroquine acts by disrupting the ability of the malarial parasite to acquire the amino acids necessary for its survival. Essentially, the medication prevents the parasite from forming a substance called hemozoin which captures the amino acids and feeds the parasite by diffusing the fluids and substances contained within the cell. Interruption of this process results in the death of the parasite. However, if the parasite does not produce hemozoin, chloroquine is not effective in treating those forms of malaria. It has much the same mechanism in the body when used to eradicate extraintestinal amebiasis through disruption of the metabolic functions of the parasite that causes that disease. It is not the most effective medication for treatment of amebiasis because so much of the dosage is absorbed in the gut and small intestine preventing enough concentration of the active agents making it to the large intestine where the parasite lives. Use of chloroquine to treat amebiasis is usually accompanied by another medication such as diloxanide furoate or a parasitic antibiotic such as paromomycin.

Since the 1950s, there has been a rise in a strain of malaria called P. falciparum that does not respond to chloroquine. There is some thought that this resistant strain developed in response to the mass distribution of chloroquine in those areas where malaria is prevalent (i.e. Southeast Asia, parts of South America, West Africa and East Africa). In these cases, chloroquine is contraindicated for treatment.

In terms of pharmacology, chloroquine is absorbed rapidly in the body through the digestive system and diffuses throughout the body in adipose tissue. Its tendency to accumulate in certain tissues in the body is the factor that contributes to many of its side effects, including the eye, liver, bloodstream or dermis.

While primarily used to prevent and treat malaria, chloroquine has proven effective in the treatment of several other conditions. Most commonly, it is used to treat extraintestinal amebiasis, an intestinal disorder caused by a parasite that may then lead to complicating conditions like dysentery or colitis. Chloroquine has also been found to have some efficacy in treating the symptoms of some autoimmune diseases like lupus and rheumatoid arthritis. Research continues in the use and application of this medication in the treatment of other diseases and conditions. There have been clinical trials around using chloroquine as a possible treatment for HIV/AIDS and other viruses that respond to antiviral agents. There has also been some promising research in chloroquine's efficacy as a possible anticancer agent.

Chloroquine interacts with many other medications, particularly those often prescribed for stomach acid issues such as acid reflux or GERD. The magnesium contained in these antacids can prevent the active ingredients in chloroquine from being absorbed in the body making it less effective. It also interacts negatively with many common over the counter medications such as acetaminophen and aspirin. In total, chloroquine interacts with over 520 medications.

It is very important that patients take chloroquine exactly as it has been prescribed by the physician. The whole dosage must be ingested for effective treatment of malaria, but it can be very dangerous if the patient takes too much of it. Overdoses of chloroquine can be fatal. If overdose is suspected, emergency medical treatment is critical. Symptoms of overdose include seizures, shallow breathing, irregular heartbeat and coma.

Chloroquine can also cause complications with certain diseases that a patient may already have. These diseases include oculotoxicity, which is a host of conditions that affect the eye, specifically the retina. Patients who already have vision issues should only take chloroquine if absolutely necessary. For patients with porphyria, chloroquine may make the symptoms of the disease worse. It can also exacerbate bone marrow suppression in patients who have a pre-existing issue with their hematologic system. Chloroquine can also worsen hearing loss in patients who already have some auditory nerve damage. It can also create a greater risk of seizures in patients with epilepsy. There is also a moderate risk of worsening liver disease in patients with impaired liver function. Chloroquine can also cause an attack of psoriasis in those patients with the condition.

Conditions treated

  •  Malaria (Acute)
  •  Extraintestinal Amebiasis
  •  Rheumatoid Arthritis
  •  Discoid Lupus Erthematosus
  •  Sarcoidosis
  •  Porphyria Cutanea Tarda
  •  Plasmodium Infections

Type of medicine

  • Diphosphate salt, quinoline, antimalarial
  • 4-aminoquinoline

Side effects

The taking of chloroquine does carry the risk of side effects. Mild to moderate side effects include:

  • Changes in hair color
  • Nausea
  •  Diarrhea
  •  Blurred vision
  •  Muscular weakness
  •  Hair loss
  •  Vomiting
  •  Headache
  •  Stomach cramps
  •  Abdominal pain
  •  Sweating

Patients should contact their physician if they experience some of the more significant side effects:

  •  Sun sensitivity
  • Extreme fatigue
  • Bruising easily
  • Excessive bleeding
  • Darkening of skin pigment
  • Swelling of legs
  • A persistent sore throat
  • Shortness of breath
  • Swelling of ankles
  • Changes in tissue inside the mouth
  • Rash or other skin sensitivity
  • Extreme weakness of muscles
  • Pale skin or lips
  • Hearing loss or ringing in the ears
  • depression
  • Severe abdominal pain
  • Dark urine
  • Rapid changes in mood
  • Jaundice or yellowing of eyes
  • Muscle twitches, particularly in the face
  • Confusion
  • Chest pain
  • Swollen glands
  • Dizziness or impaired depth perception
  • Irregular heartbeat
  • Myopathy of skeletal muscles

Patients should immediately discontinue use of chloroquine and seek immediate medical attention in the event that they experience any of the following symptoms:

  • Loss of coordination
  • Convulsions and seizures
  • Difficulty reading
  • Clay colored stool
  • Hazy vision
  • Loss of reflexes
  • Hearing loss
  • Loss of appetite
  • Ringing in the ears
  • Dark urine
  • Significant skin rash that spreads, with blisters and peeling
  • Hives
  • Polyneuritis
  • pruritus

Chloroquine can cause an allergic reaction in some patients that may require emergency medical treatment. Reactions may include swelling of the face or throat and difficulty breathing or wheezing. Patients may also have a serious skin rash with fever and blisters.

Use of chloroquine over long periods of time has been linked to damage to the retina. This damage can be irreversible and quite serious, taking the forms of conditions such as macular degeneration, scotomata, or maculopathy. Patients who have trouble seeing or whose vision is blurry, particularly if accompanied by seeing light streaks, should discontinue use of chloroquine and seek medical attention.

Chloroquine has also been linked to permanent hearing loss through auditory nerve damage or persistent tinnitus.

Use of chloroquine over time has been linked to the development of anorexia in patients, although this is very infrequent. This medication can cause serious digestive issues as well as depression. Those two factors may combine to create the conditions for the onset of eating disorders.

In rare cases, prolonged use of chloroquine has been known to cause issues with the patient's hematologic system. This includes the development of the following conditions:

  • agranulocytosis (reversible)
  • pancytopenia
  • thrombocytopenia
  • aplastic anemia
  • neutropenia

The development of one or more of these conditions is more likely if the patient already suffers from some sort of hematologic impairment. It has also been linked infrequently to the onset of hypotension and congestive heart failure.

Dosage

When used in the prevention of malaria (prophylaxis), the recommended dosage level is 500mg of chloroquine phosphate once a week, taken on the same day of each week. Treatment should begin ideally two weeks before possible exposure. Patients should continue therapy for eight weeks after leaving the area of exposure.

In the treatment of contracted malaria, if the patient weighs more than 132 pounds (60kgs), the recommended treatment is as follows: 600mg initially with subsequent doses of 500mg after six to eight hours. Patients should then take 500mg once daily for the following two days. Their total intake of chloroquine should be 2.5 grams over three days.

For patients who weigh less than 132 pounds (60kg), the dose is lower. The initial dose is 16.7mg followed by an 8.3mg dose 6 hours later. The third dose is another 8.3mg, and 36 hours after the first dose, the final dose is another 8.3mg of Chloroquine phosphate. Total dosage level should not exceed 41.7mg over 3 days.

Pediatric patients should take the lower dose and should never take more than an adult dose. Overdosing on chloroquine can be fatal, most particularly in children. This medication is absorbed into the body quickly and so overdose can happen quickly. Pediatric patients should be closely monitored as they complete this course of treatment.

In the treatment of amebiasis, the recommended dose is one gram of Chloroquine phosphate once a day for the first two days followed by two to three weeks of a 500mg dose once a day. This treatment should be combined with an effective intestinal ambecide for better efficacy.

While the use of chloroquine in the treatment of Sarcoidosis has not been approved by the FDA, physicians can use it as a second line treatment for that condition. Standard dosing for this purpose is 250mg twice daily for a period of anywhere between four and 17 months. If there is concern over retinal damage, use should be limited to six months.

Another use of chloroquine is in the treatment of the symptoms of rheumatoid arthritis. It has been shown to be effective in the reduction of inflammation and pain caused by the disease. Standard dosing levels are 400mg daily. It may be taken once a day or divided into two doses.

Chloroquine has also proven to be effective in treating symptoms of Lupus Erythematosus, particularly in reducing inflammation around the heart and lungs and reducing pain in joints and muscles. It has also been shown to reduce lupus flares by 50%. Dosage levels are the same as in the treatment of rheumatoid arthritis at 400mg daily.

Chloroquine may also be used as a second line medication in the treatment of porphyria. Standard recommended dosage for this purpose is 125mg of chloroquine twice a week until blood levels return to normal.

For other plasmodium based infections that are not resistant to chloroquine, the use of this medication in treatment should mirror the protocol for treatment of malaria. For women who are pregnant, chloroquine may be prescribed, but physicians and patients should proceed cautiously and with close supervision of patient.

Drug Interactions

Chloroquine interacts adversely with many medications. In most cases, it decreases the efficacy of the other drug. In a few cases, the interaction increases the effect of the medication, leading to increased side effects and risk of toxicity. The list of drugs that chloroquine interacts negatively with include:

  • Abciximab
  • 4-Methoxyamphetamine
  • Acebutolol
  • 16-Bromoepiandrosterone
  • Abiraterone
  • 19-norandrostenedione
  • Acetaminophen
  • Aceclofenac
  • Acetylcholine
  • Acetylsalicylic acid
  • Acenocoumarol
  • Aclarubicin
  • Agalsidase beta
  • Adapalene
  • Acetyldigitoxin
  • Afatinib
  • Albendazole
  • Arsenic trioxide
  • Lumefantrin
  • Naltrexone
  • Bedaquiline
  • Anagrelide
  • Dolasetron
  • Auranofin
  • Lidocaine
  • Amyl nitrite
  • Bepridil
  • Amiodarone
  • Aurothioglucose
  • Sotalol
  • Clozapine
  • Ibutilide
  • Prilocaine
  • Citalopram
  • Vandetanib
  • Tramadol
  • Ivabradine
  • Epinephrine
  • Live cholera vaccine
  • Cisapride
  • Crizotinib
  • Quinidine
  • Bedaquiline
  • Fentanyl
  • Deferiprone
  • Dextromethorphan
  • Dronedarone
  • Methadone
  • Disopyramide
  • Dofetilide
  • Efavirenz
  • Prilocaine
  • Escitalopram
  • Tenofovir
  • Iloperidone
  • Panobinostat
  • Saquinovir
  • Fingolimod
  • Toremifene
  • Gatifloxacin
  • Gold sodium thiomalate
  • Ziprasidone
  • Grepafloxacin
  • Haloperidol
  • Iohexol
  • Halofantrine
  • Iopamidol
  • Ribociclib
  • Mifepristone
  • Letrozole
  • Levomethadyl acetate
  • Thioridizine
  • Metrizamide
  • Mesoridizine
  • Moxifloxacin
  • Nilotinib
  • Pimozide
  • Osimertinib
  • Papavarine
  • Procainamide
  • Pasireotide
  • Cisapride
  • Vigabatrin
  • Sparfloxacin
  • Vemurafenib

These are the medications with which chloroquine has major interactions. It has moderate interactions with 425 other medications and very mild interactivity with 23 other medicines. Patients should be sure to inform their physician of all medications they are taking given the high levels of interaction this drug has across many families of medicines.

Warnings

The largest risk in use of Chloroquine is overdose. The difference between effective dosage levels for treatment of malaria, extraintestinal amebiasis, or any of the other conditions chloroquine affects positively and the level of toxicity is very small. It is absolutely critical that patients undergoing any form of chloroquine therapy follow the prescribed treatment with fidelity. Levels of toxicity increase when combined with medications in the quinidine family, so concomitant use of these medications is contraindicated. Children are at greatest risk of poisoning and fatal overdose in the use of chloroquine.

Chloroquine does pass from mother to infant in breast milk, so the use of this medication by nursing mothers is not recommended. It has not been proven to affect the fetus, so pregnant mothers may be prescribed chloroquine under close medical supervision.

In some cases, particularly where dosage levels are incorrect, chloroquine may cause severe gastrointestinal side effects, especially diarrhea which may lead to other complications such as dehydration that put the compromised patient at greater risk.

Another side effect that may result in permanent damage is the effects of chloroquine on the human eye. Damage to the retina caused by the medication is generally irreversible and can be quite significant. Regular visual screenings are important to avoid the onset of conditions such as macular degeneration or maculopathy, most especially if patients are prescribed chloroquine over long periods of time as the active agents in the drug accumulate over time in tissue like the eye.

Chloroquine should not be prescribed to patients who suffer from liver impairment. Use of this medication has been linked to the development of hepatitis and a negative effect on enzymes that could further damage liver function.

Chloroquine is contraindicated for anyone who suffers from a level of renal impairment. This drug has been shown to cause further damage to kidneys and renal function, particularly when used beyond the initial treatment period. The same is true for patients with compromised vision.

Chloroquine can also affect mental function, causing depression, anxiety, disorientation and other mental health conditions. Therefore the use of chloroquine is contraindicated for patients who already suffer from one or more of these conditions or any significant neurological issue. It is also not recommended for patients who are deficient in glucose-6-phosphate dehydrogenase.

Disposal of chloroquine must be handled carefully as well. It should not be flushed down a toilet or dumped into landfills. The most appropriate method to deal with unused medication is through a medication take-back program through a pharmacy or other medical facility. Because of the significant dangers posed by an accidental overdose of chloroquine, it cannot be disposed of in a location where it could be accidentally consumed by adults, children or animals.

In the event of overdose, immediate emergency care is vital. Chloroquine is absorbed rapidly by the body, so consequences of overdose occur rapidly, including potential cardiac failure, respiratory failure, coma and death. Immediate treatments may require gastric lavage as well as mechanical ventilation and respiratory support. Use of the medication Diazepam administered through an IV may be used to control convulsive activity and seizures.

Storage

Chloroquine comes in tablet form in several strengths: 125 mg, 250 mg and 500mg. This form is actually a combination of chloroquine and phosphate, a salt base which helps with the absorption of the medication. This medication should be kept in the original container and be tightly sealed at all times. It should be maintained at room temperature in a space that does not have excessive light, heat or moisture. It is not recommended to store this medication in the bathroom area of a home.

For medical facilities, chloroquine may be shipped in powder form at room temperature. It should be maintained at room temperature until mixed with suspension and stored away from light. Once mixed into suspension, it should be kept refrigerated and is stable for one month. As long as it is in powder form, it is good for six months.

The risk of overdose with chloroquine is very dangerous and often fatal. This medication should be kept in a secure location away from the reach of children and pets. It is also very important that any unused chloroquine is disposed of properly, either through a medication take-back program or some other safe route of disposal that would prevent the medication from accidental consumption. For more information regarding secure storage and safe disposal of chloroquine or any other medication, patients should consult the Safe Disposal of Medicines site sponsored by the FDA.

Summary

Chloroquine represents a valuable tool in the fight against malaria, and that remains its primary use globally. It is a member of the aminoquinoline family and has both anti-parasitic and anti-inflammatory properties. As a treatment for malaria, it has been available since World War II. Because of its effects on the human body, it can be used to treat a variety of diseases and conditions from parasitic conditions like malaria and extraintestinal amebiasis to autoimmune disorders such as lupus and rheumatoid arthritis. Currently, research is being conducted at various levels to determine chloroquine's efficacy in treating other families of disease including HIV/AIDS and other viral infections as well as some forms of cancer.

Chloroquine is a powerful medication and carries with it the risk of many side effects. Some of those side effects are fairly minor such as a headache or abdominal discomfort. Others, including macular degeneration, hearing loss and anaphylaxis, are very significant as well as potentially fatal.

This medication is usually delivered in tablet form, with a typical dosage of 500mg daily. It can be given as an injection, particularly in treating an acute malarial infection. Tablets should be kept at room temperature in the original container and tightly sealed at all times. Medication should be protected from exposure to sunlight and moisture. When in suspension for IV delivery, it should be refrigerated and used within 24 hours.

The use and disposal of this medication must be followed according to direction from the medical care provider, physician and/or pharmacist. Chloroquine can be a dangerous drug when used inappropriately or accidentally, so secure storage and appropriate disposal of extra or unused medication is indicated. It is also very important that instructions for taking the medication are well explained and well understood by the patient before treatment protocol begins. Patients must closely follow the prescription instructions and take the full course of the medication for the regimen to be effective.

Once dosage levels for treatment of malaria were established during World War II, chloroquine was used as a front-line treatment for the disease, but it has also been used as a preventative treatment for malaria. While this has proven effective, it has also led to a rise in resistant forms of the disease. Today, chloroquine is no longer the first choice in the treatment of malaria. It is only effective in about one-third of all current malaria cases. Chloroquine continues to be a resource in the fight against malaria but is actually more commonly used now for treatment of other diseases. There are some promising possibilities for other applications for chloroquine.